Purpose: In REPLACE, patients with pulmonary arterial hypertension (PAH) at intermediate risk despite phosphodiesterase-5 inhibitor (PDE5i) treatment achieved clinical improvement when switched to riociguat compared with those who continued PDE5i. Significant improvements in risk status with riociguat versus PDE5i maintenance were seen using the three-strata COMPERA risk assessment tool. COMPERA 2.0 is a new four-strata tool designed to be more sensitive to prognostically relevant changes in risk. We applied COMPERA 2.0 to REPLACE post hoc to investigate potential differences in outcomes between intermediate–low-risk and intermediate–high-risk patients.
Methods: COMPERA 2.0 scores at baseline and week 24, and change from baseline, were calculated. Response (achievement of the REPLACE primary endpoint at week 24) and clinical worsening were assessed in patients categorized as intermediate–low and intermediate–high risk by COMPERA 2.0 at baseline.
Results: At baseline in the riociguat (n = 111) and PDE5i (n = 113) groups, 60% and 55% of patients were intermediate–low risk and 40% and 45% were intermediate–high risk, respectively. Improvement in COMPERA 2.0 from baseline to week 24 was significantly higher with riociguat versus PDE5i [45% vs. 25%, respectively; mean difference (95% confidence interval) 0.23 (0.05 to 0.41); P = 0.0059]. At week 24, 28% of riociguat-treated patients and 12% of PDE5i-treated patients improved to low-risk status. A similar percentage of intermediate–low-risk patients (riociguat, 39%; PDE5i, 19%) and intermediate–high-risk patients (riociguat, 43%; PDE5i, 22%) achieved the primary endpoint at week 24. All intermediate–low-risk and intermediate–high-risk responders showed significant improvements in COMPERA 2.0 at week 24 versus baseline and versus non-responders. All patients who died or experienced clinical worsening were intermediate–high risk at baseline.
Conclusions: Patients with PAH at intermediate–low risk and intermediate–high risk by COMPERA 2.0 at baseline achieved similar clinical improvement when switching to riociguat from PDE5i therapy in REPLACE. COMPERA 2.0 provides a risk assessment approach for better differentiating the large group of patients at intermediate risk.
Disclosures: The REPLACE study was co-funded by Bayer AG (Berlin, Germany) and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (Kenilworth, NJ, USA). R.L.B. reports grants from Actelion, Bellerophon, Bayer AG and EIGER.
R. L. Benza, Division of Cardiovascular Diseases, Ohio State University, Columbus, OH, USA G. Simonneau, Assistance Publique–Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Université Paris-Saclay, Laboratoire d’Excellence en Recherche sur le Médicament et Innovation Thérapeutique, and Inserm U999, Le Kremlin-Bicêtre, France H. A. Ghofrani, University of Giessen and Marburg Lung Center, member of the German Center for Lung Research (DZL), Giessen, Germany, Department of Pneumology, Kerckhoff Clinic, Bad Nauheim, Germany, and Department of Medicine, Imperial College London, London, UK P. A. Corris, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK S. Rosenkranz, Clinic III for Internal Medicine (Cardiology), Cologne Cardiovascular Research Center (CCRC), and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany D. Langleben, Center for Pulmonary Vascular Disease and Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, QC, Canada C. Meier, Global Medical Affairs, Bayer AG, Berlin, Germany C. Rahner, Chrestos Concept GmbH & Co. KG, Essen, Germany M. M. Hoeper, Clinic for Respiratory Medicine, Hannover Medical School, member of the German Center for Lung Research (DZL), Hannover, Germany